期刊
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
卷 10, 期 3, 页码 393-404出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2014.1721
关键词
Radiolabeled Gold Nanospheres; RGD Peptides; Lutetium-177; Targeted Radiotherapy
资金
- Mexican National Council of Science and Technology [CONACYT-SEP-CB-2010-01-150942]
Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of alpha(v)beta(3) integrin, thereby inhibiting angiogenesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable multimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of Lu-177-AuNP-RGD in athymic mice bearing alpha(v)beta(3)-integrin-positive C6 gliomas and compare it with that of Lu-177-AuNP or Lu-177-RGD. The radiation absorbed dose, metabolic activity (SUV, [F-18]fluor-deoxy-glucose-microPET/CT), histological characteristics and VEGF gene expression (by real-time polymerase chain reaction) in tumor tissues following treatment with Lu-177-AuNP-RGD, Lu-177-AuNP or Lu-177-RGD were assessed. Of the radiopharmaceuticals evaluated, Lu-177-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 +/- 7.9 Gy). These results correlated with the observed therapeutic response, in which Lu-177-AuNP-RGD significantly (p < 0.05) induced less tumor progression, less tumor metabolic activity, fewer intratumoral vessels and less VEGF gene expression than the other radiopharmaceuticals, a consequence of high tumor retention and a combination of molecular targeting therapy (multimeric RGD system) and radiotherapy (Lu-177). There was a low uptake in non-target organs and no induction of renal toxicity. Lu-177-labeled gold nanoparticles conjugated to cyclo-RGDfK(C) demonstrate properties suitable for use as an agent for molecular targeting radiotherapy.
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